Neurons, Synapses, and Signaling Chapter 48 Neurons, Synapses, and Signaling

Sensors detect external stimuli and internal conditions and transmit information along sensory neurons Sensory information is sent to the brain or ganglia, where interneurons integrate the information Motor output leaves the brain or ganglia via motor neurons, which trigger muscle or gland activity

Many animals have a complex nervous system which consists of: A central nervous system (CNS) where integration takes place; this includes the brain and a nerve cord A peripheral nervous system (PNS), which brings information into and out of the CNS

Peripheral nervous system (PNS) Central nervous system (CNS) Fig. 48-3 Sensory input Integration Sensor Motor output Figure 48.3 Summary of information processing The transmission of information depends on the path of neurons along which a signal travels Processing of information takes place in simple clusters of neurons called ganglia or a more complex organization of neurons called a brain Nervous systems process information in three stages: sensory input, integration, and motor output Effector Peripheral nervous system (PNS) Central nervous system (CNS)

Neuron Structure and Function Most of a neuron’s organelles are in the cell body Most neurons have dendrites, highly branched extensions that receive signals from other neurons The axon is typically a much longer extension that transmits signals to other cells at synapses An axon joins the cell body at the axon hillock

Dendrites Stimulus Presynaptic Nucleus cell Axon hillock Cell body Fig. 48-4 Dendrites Stimulus Nucleus Presynaptic cell Axon hillock Cell body Axon Synapse Synaptic terminals Figure 48.4 Neuron structure and organization For the Cell Biology Video Dendrites of a Neuron, go to Animation and Video Files. Postsynaptic cell Neurotransmitter

A synapse is a junction between an axon and another cell The synaptic terminal of one axon passes information across the synapse in the form of chemical messengers called neurotransmitters

Information is transmitted from a presynaptic cell (a neuron) to a postsynaptic cell (a neuron, muscle, or gland cell) Most neurons are nourished or insulated by cells called glia

Dendrites Axon Cell body Sensory neuron Fig. 48-5a Figure 48.5 Structural diversity of neurons Sensory neuron

Portion of axon Cell bodies of overlapping neurons Interneurons 80 µm Fig. 48-5b Figure 48.5 Structural diversity of neurons Portion of axon 80 µm Cell bodies of overlapping neurons Interneurons

Concept 48.2: Ion pumps and ion channels maintain the resting potential of a neuron Every cell has a voltage (difference in electrical charge) across its plasma membrane called a membrane potential Messages are transmitted as changes in membrane potential The resting potential is the membrane potential of a neuron not sending signals

Formation of the Resting Potential In a mammalian neuron at resting potential, the concentration of K+ is greater inside the cell, while the concentration of Na+ is greater outside the cell Sodium-potassium pumps use the energy of ATP to maintain these K+ and Na+ gradients across the plasma membrane These concentration gradients represent chemical potential energy

The opening of ion channels in the plasma membrane converts chemical potential to electrical potential A neuron at resting potential contains many open K+ channels and fewer open Na+ channels; K+ diffuses out of the cell Anions trapped inside the cell contribute to the negative charge within the neuron

[Na+] 150 mM [Cl–] 120 mM [K+] 140 mM [A–] 100 mM Fig. 48-6 Key Na+ Sodium- potassium pump Potassium channel Sodium channel K+ OUTSIDE CELL OUTSIDE CELL [K+] 5 mM [Na+] 150 mM [Cl–] 120 mM INSIDE CELL [K+] 140 mM [Na+] 15 mM [Cl–] 10 mM [A–] 100 mM Figure 48.6 The basis of the membrane potential INSIDE CELL (a) (b)

150 mM 120 mM [K+] 140 mM [A–] 100 mM (a) OUTSIDE CELL INSIDE CELL Fig. 48-6a OUTSIDE CELL [K+] 5 mM [Na+] 150 mM [Cl–] 120 mM INSIDE CELL [K+] 140 mM [Na+] 15 mM [Cl–] 10 mM [A–] 100 mM Figure 48.6a The basis of the membrane potential (a)

Key Na+ Sodium- potassium Potassium Sodium pump channel channel K+ Fig. 48-6b Key Na+ Sodium- potassium pump Potassium channel Sodium channel K+ OUTSIDE CELL Figure 48.6b The basis of the membrane potential INSIDE CELL (b)

Modeling of the Resting Potential Resting potential can be modeled by an artificial membrane that separates two chambers The concentration of KCl is higher in the inner chamber and lower in the outer chamber K+ diffuses down its gradient to the outer chamber Negative charge builds up in the inner chamber At equilibrium, both the electrical and chemical gradients are balanced The process of moving sodium and potassium ions across the cell membrance is an active transport process involving the hydrolysis of ATP to provide the necessary energy. It involves an enzyme referred to as Na+/K+-ATPase. This process is responsible for maintaining the large excessof Na+ outside the cell and the large excess of K+ ions on the inside. A cycle of the transport process is sketched below. It accomplishes the transport of three Na+ to the outside of the cell and the transport of two K+ ions to the inside. This unbalanced charge transfer contributes to the separation of charge across the membrane. The sodium-potassium pump is an important contributer to action potential produced by nerve cells. This pump is called a P-type ion pump because the ATP interactions phosphorylates the transport protein and causes a change in its conformation.

( ) ( ) KCI NaCI 140 mM 150 mM Inner chamber –90 mV Outer chamber Fig. 48-7 Inner chamber –90 mV Outer chamber +62 mV 140 mM 5 mM 15 mM 150 mM KCI NaCI KCI NaCI Cl– K+ Na+ Cl– Sodium channel Potassium channel Figure 48.7 Modeling a mammalian neuron (a) Membrane selectively permeable to K+ (b) Membrane selectively permeable to Na+ ( ) ( ) 5 mM 150 mM EK = 62 mV log = –90 mV ENa = 62 mV log = +62 mV 140 mM 15 mM

( ) 140 mM KCI 5 mM EK = 62 mV log = –90 mV 140 mM –90 mV Inner Outer Fig. 48-7a Inner chamber –90 mV Outer chamber 140 mM 5 mM KCI KCI K+ Cl– Potassium channel Figure 48.7a Modeling a mammalian neuron (a) Membrane selectively permeable to K+ ( ) 5 mM EK = 62 mV log = –90 mV 140 mM

The equilibrium potential (Eion) is the membrane voltage for a particular ion at equilibrium and can be calculated using the Nernst equation: Eion = 62 mV (log[ion]outside/[ion]inside) The equilibrium potential of K+ (EK) is negative, while the equilibrium potential of Na+ (ENa) is positive

In a resting neuron, the currents of K+ and Na+ are equal and opposite, and the resting potential across the membrane remains steady

( ) 150 mM NaCI +62 mV ENa = 62 mV = +62 mV 15 mM Sodium channel Fig. 48-7b +62 mV 15 mM 150 mM NaCI NaCI Cl– Na+ Sodium channel Figure 48.7b Modeling a mammalian neuron (b) Membrane selectively permeable to Na+ ( ) 150 mM ENa = 62 mV log = +62 mV 15 mM

Concept 48.3: Action potentials are the signals conducted by axons Neurons contain gated ion channels that open or close in response to stimuli

TECHNIQUE Microelectrode Voltage recorder Reference electrode Fig. 48-8 TECHNIQUE Microelectrode Voltage recorder Figure 48.8 Intracellular recording Reference electrode

Membrane potential changes in response to opening or closing of these channels When gated K+ channels open, K+ diffuses out, making the inside of the cell more negative This is hyperpolarization, an increase in magnitude of the membrane potential

Figure 48.9 Graded potentials and an action potential in a neuron Stimuli Stimuli Strong depolarizing stimulus +50 +50 +50 Action potential Membrane potential (mV) Membrane potential (mV) Membrane potential (mV) –50 Threshold –50 Threshold –50 Threshold Resting potential Resting potential Resting potential Figure 48.9 Graded potentials and an action potential in a neuron Hyperpolarizations Depolarizations –100 –100 –100 1 2 3 4 5 1 2 3 4 5 1 2 3 4 5 6 Time (msec) Time (msec) Time (msec) (a) Graded hyperpolarizations (b) Graded depolarizations (c) Action potential

Membrane potential (mV) Fig. 48-9a Stimuli +50 Membrane potential (mV) –50 Threshold Figure 48.9a Graded potentials and an action potential in a neuron Resting potential Hyperpolarizations –100 1 2 3 4 5 Time (msec) (a) Graded hyperpolarizations

Other stimuli trigger a depolarization, a reduction in the magnitude of the membrane potential For example, depolarization occurs if gated Na+ channels open and Na+ diffuses into the cell Graded potentials are changes in polarization where the magnitude of the change varies with the strength of the stimulus

Membrane potential (mV) Fig. 48-9b Stimuli +50 Membrane potential (mV) –50 Threshold Figure 48.9b Graded potentials and an action potential in a neuron Resting potential Depolarizations –100 1 2 3 4 5 Time (msec) (b) Graded depolarizations

Production of Action Potentials Voltage-gated Na+ and K+ channels respond to a change in membrane potential When a stimulus depolarizes the membrane, Na+ channels open, allowing Na+ to diffuse into the cell The movement of Na+ into the cell increases the depolarization and causes even more Na+ channels to open A strong stimulus results in a massive change in membrane voltage called an action potential

Strong depolarizing stimulus Fig. 48-9c Strong depolarizing stimulus +50 Action potential Membrane potential (mV) –50 Threshold Figure 48.9c Graded potentials and an action potential in a neuron Resting potential –100 1 2 3 4 5 6 Time (msec) (c) Action potential

An action potential occurs if a stimulus causes the membrane voltage to cross a particular threshold An action potential is a brief all-or-none depolarization of a neuron’s plasma membrane Action potentials are signals that carry information along axons

A neuron can produce hundreds of action potentials per second Fig. 48-10-1 Key Na+ K+ +50 Action potential 3 Membrane potential (mV) 2 4 Threshold –50 1 1 5 Resting potential Depolarization –100 Figure 48.10 The role of voltage-gated ion channels in the generation of an action potential A neuron can produce hundreds of action potentials per second The frequency of action potentials can reflect the strength of a stimulus An action potential can be broken down into a series of stages Time Extracellular fluid Sodium channel Potassium channel Plasma membrane Cytosol Inactivation loop 1 Resting state

Fig. 48-10-2 Key Na+ K+ +50 Action potential 3 Membrane potential (mV) 2 4 Threshold –50 1 1 5 Resting potential 2 Depolarization –100 Figure 48.10 The role of voltage-gated ion channels in the generation of an action potential Time Extracellular fluid Sodium channel Potassium channel Plasma membrane Cytosol Inactivation loop 1 Resting state

Fig. 48-10-3 Key Na+ K+ 3 Rising phase of the action potential +50 Action potential 3 Membrane potential (mV) 2 4 Threshold –50 1 1 5 Resting potential 2 Depolarization –100 Figure 48.10 The role of voltage-gated ion channels in the generation of an action potential Time Extracellular fluid Sodium channel Potassium channel Plasma membrane Cytosol Inactivation loop 1 Resting state

Fig. 48-10-4 Key Na+ K+ 3 Rising phase of the action potential 4 Falling phase of the action potential +50 Action potential 3 Membrane potential (mV) 2 4 Threshold –50 1 1 5 Resting potential 2 Depolarization –100 Figure 48.10 The role of voltage-gated ion channels in the generation of an action potential Time Extracellular fluid Sodium channel Potassium channel Plasma membrane Cytosol Inactivation loop 1 Resting state

Fig. 48-10-5 Key Na+ K+ 3 Rising phase of the action potential 4 Falling phase of the action potential +50 Action potential 3 Membrane potential (mV) 2 4 Threshold –50 1 1 5 Resting potential 2 Depolarization –100 Figure 48.10 The role of voltage-gated ion channels in the generation of an action potential Time Extracellular fluid Sodium channel Potassium channel Plasma membrane Cytosol Inactivation loop 5 Undershoot 1 Resting state

At resting potential Most voltage-gated Na+ and K+ channels are closed, but some K+ channels (not voltage-gated) are open

When an action potential is generated Voltage-gated Na+ channels open first and Na+ flows into the cell During the rising phase, the threshold is crossed, and the membrane potential increases During the falling phase, voltage-gated Na+ channels become inactivated; voltage-gated K+ channels open, and K+ flows out of the cell

During the undershoot, membrane permeability to K+ is at first higher than at rest, then voltage-gated K+ channels close; resting potential is restored

BioFlix: How Neurons Work Animation: Action Potential During the refractory period after an action potential, a second action potential cannot be initiated The refractory period is a result of a temporary inactivation of the Na+ channels BioFlix: How Neurons Work Animation: Action Potential

Conduction of Action Potentials An action potential can travel long distances by regenerating itself along the axon At the site where the action potential is generated, usually the axon hillock, an electrical current depolarizes the neighboring region of the axon membrane

Inactivated Na+ channels behind the zone of depolarization prevent the action potential from traveling backwards Action potentials travel in only one direction: toward the synaptic terminals

Figure 48.11 Conduction of an action potential Axon Plasma membrane Action potential Na+ Cytosol Figure 48.11 Conduction of an action potential

Figure 48.11 Conduction of an action potential Axon Plasma membrane Action potential Na+ Cytosol Action potential K+ Na+ Figure 48.11 Conduction of an action potential K+

Figure 48.11 Conduction of an action potential Axon Plasma membrane Action potential Na+ Cytosol Action potential K+ Na+ Figure 48.11 Conduction of an action potential K+ Action potential K+ Na+ K+

Conduction Speed The speed of an action potential increases with the axon’s diameter In vertebrates, axons are insulated by a myelin sheath, which causes an action potential’s speed to increase Myelin sheaths are made by glia— oligodendrocytes in the CNS and Schwann cells in the PNS

Figure 48.12 Schwann cells and the myelin sheath Node of Ranvier Layers of myelin Axon Schwann cell Schwann cell Nodes of Ranvier Nucleus of Schwann cell Axon Myelin sheath Figure 48.12 Schwann cells and the myelin sheath 0.1 µm

Node of Ranvier Layers of myelin Axon Schwann cell Schwann cell Fig. 48-12a Node of Ranvier Layers of myelin Axon Schwann cell Schwann cell Figure 48.12 Schwann cells and the myelin sheath Nodes of Ranvier Nucleus of Schwann cell Axon Myelin sheath

Action potentials are formed only at nodes of Ranvier, gaps in the myelin sheath where voltage-gated Na+ channels are found Action potentials in myelinated axons jump between the nodes of Ranvier in a process called saltatory conduction

Schwann cell Depolarized region (node of Ranvier) Cell body Myelin Fig. 48-13 Schwann cell Depolarized region (node of Ranvier) Cell body Myelin sheath Axon Figure 48.13 Saltatory conduction

Concept 48.4: Neurons communicate with other cells at synapses At electrical synapses, the electrical current flows from one neuron to another At chemical synapses, a chemical neurotransmitter carries information across the gap junction Most synapses are chemical synapses

Postsynaptic neuron Synaptic terminals of pre- synaptic neurons 5 µm Fig. 48-14 Postsynaptic neuron Synaptic terminals of pre- synaptic neurons Figure 48.14 Synaptic terminals on the cell body of a postsynaptic neuron (colorized SEM) 5 µm

Synapse Synaptic vesicles containing Presynaptic neurotransmitter Fig. 48-15 5 Na+ K+ Synaptic vesicles containing neurotransmitter Presynaptic membrane Voltage-gated Ca2+ channel Postsynaptic membrane 1 Ca2+ 4 2 6 Synaptic cleft 3 Figure 48.15 A chemical synapse Ligand-gated ion channels Synapse

Generation of Postsynaptic Potentials Direct synaptic transmission involves binding of neurotransmitters to ligand-gated ion channels in the postsynaptic cell Neurotransmitter binding causes ion channels to open, generating a postsynaptic potential

Postsynaptic potentials fall into two categories: Excitatory postsynaptic potentials (EPSPs) are depolarizations that bring the membrane potential toward threshold Inhibitory postsynaptic potentials (IPSPs) are hyperpolarizations that move the membrane potential farther from threshold

After release, the neurotransmitter May diffuse out of the synaptic cleft May be taken up by surrounding cells May be degraded by enzymes

Summation of Postsynaptic Potentials Unlike action potentials, postsynaptic potentials are graded and do not regenerate Most neurons have many synapses on their dendrites and cell body A single EPSP is usually too small to trigger an action potential in a postsynaptic neuron If two EPSPs are produced in rapid succession, an effect called temporal summation occurs

Figure 48.16 Summation of postsynaptic potentials Terminal branch of presynaptic neuron E1 E1 E1 E1 E2 E2 E2 E2 Postsynaptic neuron Axon hillock I I I I Threshold of axon of postsynaptic neuron Action potential Action potential Membrane potential (mV) Resting potential –70 Figure 48.16 Summation of postsynaptic potentials E1 E1 E1 E1 E1 + E2 E1 I E1 + I (a) Subthreshold, no summation (b) Temporal summation (c) Spatial summation (d) Spatial summation of EPSP and IPSP

E1 E1 E2 E2 I I E1 E1 E1 E1 Terminal branch of presynaptic neuron Fig. 48-16ab Terminal branch of presynaptic neuron E1 E1 E2 E2 Postsynaptic neuron Axon hillock I I Threshold of axon of postsynaptic neuron Action potential Membrane potential (mV) Resting potential Figure 48.16a,b Summation of postsynaptic potentials –70 E1 E1 E1 E1 (a) Subthreshold, no summation (b) Temporal summation

In spatial summation, EPSPs produced nearly simultaneously by different synapses on the same postsynaptic neuron add together The combination of EPSPs through spatial and temporal summation can trigger an action potential

E1 E1 E2 E2 I I –70 E1 + E2 E1 I E1 + I (c) Spatial summation Fig. 48-16cd E1 E1 E2 E2 I I Action potential Membrane potential (mV) Figure 48.16c,d Summation of postsynaptic potentials –70 E1 + E2 E1 I E1 + I (c) Spatial summation (d) Spatial summation of EPSP and IPSP

Through summation, an IPSP can counter the effect of an EPSP The summed effect of EPSPs and IPSPs determines whether an axon hillock will reach threshold and generate an action potential

Modulated Synaptic Transmission In indirect synaptic transmission, a neurotransmitter binds to a receptor that is not part of an ion channel This binding activates a signal transduction pathway involving a second messenger in the postsynaptic cell Effects of indirect synaptic transmission have a slower onset but last longer

Neurotransmitters The same neurotransmitter can produce different effects in different types of cells There are five major classes of neurotransmitters: acetylcholine, biogenic amines, amino acids, neuropeptides, and gases

Table 48-1 Table 48.1

Table 48-1a Table 48.1

Table 48-1b Table 48.1

Acetylcholine Acetylcholine is a common neurotransmitter in vertebrates and invertebrates In vertebrates it is usually an excitatory transmitter

Biogenic Amines Biogenic amines include epinephrine, norepinephrine, dopamine, and serotonin They are active in the CNS and PNS

Amino Acids Two amino acids are known to function as major neurotransmitters in the CNS: gamma-aminobutyric acid (GABA) and glutamate

Neuropeptides Several neuropeptides, relatively short chains of amino acids, also function as neurotransmitters Neuropeptides include substance P and endorphins, which both affect our perception of pain Opiates bind to the same receptors as endorphins and can be used as painkillers